Hydrogen gas inhibits lung cancer progression through targeting SMC3

Biomed Pharmacother. 2018 Aug;104:788-797. doi: 10.1016/j.biopha.2018.05.055. Epub 2018 May 29.

Abstract

Lung cancer is one of the most common lethal malignancies in the globe. The patients' prognoses are dim due to its high metastatic potential and drug resistance. Therefore, in the present study, we aim to find a more potent therapeutic approach for lung cancer. We mainly explored the function of hydrogen gas (H2) on cell viability, apoptosis, migration and invasion in lung cancer cell lines A549 and H1975 by CCK-8, flow cytometry, wound healing and transwell assays, respectively. We used RNA-seq, qPCR and western blotting to detect the different expression genes (DEGs) between H2 group and control group to find the gene related to chromosome condensation. Besides, we confirmed the structural maintenance of chromosomes 3 (SMC3) and H2 on the progression of lung cancer in vitro and vivo. Results showed that H2 inhibited cell viability, migration and invasion, and catalyzed cell apoptosis and H2 induced A549 and H1975 cells G2/M arrest. Besides, H2 down-regulated the expression of NIBPL, SMC3, SMC5 and SMC6, and also reduced the expression of Cyclin D1, CDK4 and CDK6. H2 translocated the subcellular location of SMC3 during cell division and decreased its stability and increased its ubiquitination in both A549 and H1975 cells. In addition, inhibition of the proliferation, migration and invasion and promotion of the apoptosis of A549 and H1975 cells induced by H2 were all abolished when overexpressed SMC3 in the presence of H2. Animal experimental assay demonstrated that the tumor weight in H2 group was significantly smaller than that in control group, but was bigger than cis-platinum group. The expression of Ki-67, VEGF and SMC3 were decreased when mice were treated with H2 or cis-platinum, especially for cis-platinum. All data suggested that H2 inhibited lung cancer progression through down-regulating SMC3, a regulator for chromosome condensation, which provided a new method for the treatment of lung cancer.

Keywords: Chromosome condensation; Hydrogen gas; Lung cancer; SMC3.

MeSH terms

  • A549 Cells
  • Animals
  • Apoptosis / drug effects
  • Cell Cycle Proteins / metabolism*
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Chondroitin Sulfate Proteoglycans / metabolism*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Down-Regulation / drug effects
  • G2 Phase / drug effects
  • Humans
  • Hydrogen / pharmacology*
  • Ki-67 Antigen / metabolism
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness / pathology
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Cell Cycle Proteins
  • Chondroitin Sulfate Proteoglycans
  • Chromosomal Proteins, Non-Histone
  • Ki-67 Antigen
  • SMC3 protein, human
  • Vascular Endothelial Growth Factor A
  • Hydrogen